Loading...
 

January - March 2009: 
Volume 22, Issue 1

Click on the image to download the Issue in PDF format.

ARCHIVE

Βacteriology of pleural infection. «Streptococcus milleri group» in the limelight
Abstract
SUMMARY. Bacterial infection of the pleura is an old disease that continues to have a considerable mortality, of >15%. It is more common in males, and in the presence of diabetes mellitus, malignancy and alcoholism. The bacteriology of pleural infection has been changing during the past decades. Although pleural fluid culture is the «gold standard» for the identification of microorganisms in the pleural fluid, molecular methods such as polymerase chain reaction (PCR) have a notably higher sensitivity (75% versus 60%). Community-acquired pleural infection (CAPI) and hospital-acquired pleural infection (HAPI) have substantial differences in both their bacteriology and mortality, while the bacteriology of both differs markedly from that of pneumonia. The «Streptococcus milleri group» is the predominant isolate in CAPI, followed by Streptococcus pneumoniae. In HAPI the most common isolates are Staphylococcus aureus, usually methicillin-resistant (MRSA), and Enterococcus spp. Given the higher incidence of CAPI compared to HAPI, «Streptococcus milleri» accounts for the greatest number of pleural infections. The «Streptococcus milleri group» consists of Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedius. The unique characteristics of these bacteria favour the production of putrifying and necrotizing infections. The most common thoracic infection due to these organisms is empyema. Drainage of the infected pleural fluid and administration of antibiotics are essential components of the management of pleural infection. Knowledge of the pleural infection bacteriology is a useful adjunct in the selection of the appropriate antibiotic treatment. Pneumon 2009; 22(1):–
Full text

Introduction

Bacterial infection of the pleura was first described in ancient Greece by Hippocrates1. It continues to affect a large number of adults, being more common in males than females (2:1), and in patients with a history of diabetes mellitus, malignancy or excessive alcohol consumption2,3. Although a variety of events, such as surgical procedures, trauma, oesophageal perforation, spontaneous pneumothorax, thoracentesis, subdiaphragmatic infection and septicaemia, may all be associated with pleural infection, pneumonia is the most common associated condition, accounting for 50-75% of cases1, 4. The overall mortality from this disease remains high, at >15%2,4,5. Hospital-acquired infections and old age are associated with higher mortality4.

Empyema and complicated parapneumonic effusion are the two main clinical syndromes associated with thoracic bacterial infections1. Both are characterized by the accumulation of large amounts of pleural fluid and the deposition of fibrin along the pleura. Thickening of the pleura limits not only CO2 diffusion out of, but also O2 diffusion into the pleural space, leading to the production of an acidic anaerobic environment in the pleural cavity1. The treatment consists primarily of drainage of the infected pleural fluid and appropriate antibiotic therapy. In addition, about 40% of cases require surgical intervention6-9. Uncomplicated parapneumonic effusions have no evidence of pleural infection and usually resolve with antibiotic treatment only1.

Studies have demonstrated that the bacteriology of pleural infection in adults has been changing over the past decades. Streptococcus pneumoniae (60-70%) and Streptococcus hemolyticus were the bacteria most commonly isolated from infected pleural fluids before the advent of antibiotics10. Between 1955 and 1965, Staphylococcus aureus became the most common isolate, to be overtaken by the anaerobic organisms in the early 1970s 10,11. In the past twenty years, aerobic organisms have again become the predominant isolates8-10. Recent studies suggest that currently the most common agent of pleural infection is the «Streptococcus milleri group»2, 7.

The aim of this review is to provide information about the current microbiology of pleural infections, focussing on the characteristic features of the «Streptococcus milleri group».

The bacteriology of pleural infection

Identification of the causative bacteria

Gram stain and culture have for decades been the «gold standard» for the detection of microorganisms in pleural fluid samples. However, conventional pleural fluid cultures, especially in the event of the prior use of antibiotics, exhibit a low sensitivity which barely reaches 60% when the samples are inoculated directly into blood culture bottles2, 14. Peripheral blood culture can increase the identification rate of the causative organism, while sputum cultures are positive less often than pleural fluid cultures7,15. A variety of other techniques, such as countercurrent immunoelectrophoresis, direct gas-liquid chromatography, immunochromatographic membrane test and flow-cytometry, have not been demonstrated to be superior, because their usefulness is limited to certain bacterial groups16-19. Currently, the use of nucleic amplification tests appears to be the method with the highest sensitivity (up to 75%) in the identification of bacteria in pleural fluid2,20. It should be emphasized, however, that pleural fluid culture is the only method that provides the sensitivity profile of the isolated microorganism to various antibiotics.

Patient group determination

Several studies during the past few years have reported an increased isolation rate of nosocomial Gram negative pathogens from infected pleural fluid in the adult population (Table 1)21,22. This observation, along with the fact that the number of hospitalized patients and residents in health-care facilities has increased in recent years suggested that there might be more than one subgroup included in the general population group. This suspicion was confirmed by the Multicenter Intrapleural Sepsis Trial (MIST1) which demonstrated that the differences in bacteriology and mortality between community-acquired pleural infection (CAPI) and hospital-acquired pleural infection (HAPI) are so significant that they should probably be considered as two separate clinical syndromes2.

Differences in the bacteriology of pleural infection between ICU and ward patient groups have also been found. The isolation rate of Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) is higher in the ICU patients3. This observation is consistent with the MIST1 finding that pleural infections due to Gram-negative bacteria or MRSA have a poorer prognosis2. However, the distinction between ICU and ward patients with pleural infection as a guide to empirical antibiotic treatment has the limitation that the need for ICU treatment is often not known at presentation. The differentiation between CAPI and HAPI, based on the patients' history, is easier.

Community-Acquired Pleural Infection (CAPI)

Few researchers have studied patients with CAPI as a distinct population. Three recent studies demonstrated Streptococcus spp as the predominant microorganisms in CAPI. In two of these studies, the «Streptococcus milleri group» was cultured in more than 30% of the patients2,7. The heterogeneous group of Streptococci viridans accounted for the majority of isolates in the third study23. However, the Streptococci viridans group encompasses the «Streptococcus milleri group». Jerng et al have shown that «Streptococcus milleri» was the main bacterial subgroup isolated from pleural infections due to Streptococci Viridans, accounting for 68% of the cases24. The cumulative results from these studies are shown in Table 2., where Streptococci viridans (4%) and Streptococci milleri (22%) are shown separately. If it is taken into account that about two thirds of Streptococci viridans are represented by Streptococci milleri, the isolation rate of the Streptococcus milleri group reaches 25%. It is interesting that the most common cause of community-acquired pneumonia (CAP), Streptococcus pneumoniae, was not the predominant isolate in CAPI.

TABLE 1. The bacteriology of pleural infection in the general population diachronically.

 

Bartlett et al
(1974)

Varkey et al
(1981)

Brook et al
(1993)

Bilgin et al
(2006)

Lin et al
(2007)

Isolates (n)

214

93

343

54

292

Aerobic Gram (+)

44

28

157

38

105

Streptococcus spp

17

17

92

14

54

S. pneumoniae

5

6

70

10

6

S. pyogenes

4

5

9

0

0

S. viridans

0

0

0

0

34

Οther streptococci

8

6

13

4

14

Staph. aureus

17

7

58

21

35

MSSA

 

 

 

 

13

MRSA

 

 

 

 

22

Enterococcus spp

5

4

4

0

15

Other Gram (+)

5

 

3

3

1

Aerobic Gram (-)

30

19

59

16

129

Klebsiella pn

6

1

16

0

37

Pseudomonas spp

10

8

9

7

29

Escherichia coli

11

4

17

6

21

Enterobacter spp

0

3

0

0

5

Proteus spp

2

1

5

0

12

S.maltophilia

0

0

0

0

5

Acinetobacter spp

0

0

0

0

5

other Gram (-)

1

2

12

3

15

Aerobic

140

46

127

0

51

Bacteroides spp

23

13

26

 

9

Prevotella spp

13

5

22

 

7

Fusobacterium

16

7

20

 

6

Peptostreptococcus

26

8

28

 

22

Anaerobic streptococci

15

4

12

 

0

other anaerobic

47

9

19

 

7

Of particular importance is the bacterial microbiology from MIST1, which was reported by Maskell et al2, studing 454 patients with pleural infection. The determination of the responsible pathogen was based on either pleural fluid culture, or nucleic acid amplification, or both. CAPI were most frequently due to streptococcal infection; the «Streptococcus milleri group» accounted for 24%, Streptococcus pneumoniae for 21% and other streptococcal species for 7%. Anaerobic and Gram negative bacteria were responsible for the 25% and 9% of the cases, respectively.

Similar results were reported by Ahmed et al in 16 patients with CAPI in Canada7; of 3,675 patients with CAP, 24 (0.7%) were diagnosed with pleural infection, and pleural fluid culture was positive in 16 (67%) of these. The «Streptococcus milleri group» was the most common pathogen, isolated in 50% of these patients. Other streptococci species including group A and group G streptococci were isolated in 19%. Anaerobic bacteria, Klebsiella pneumoniae, mixed bacteria flora, and Candida albicans were isolated in 6% each.

Finally, Liang et al 23 reported that the most commonly isolated organisms in 46 young adult patients with CAPI were Streptococci viridans (27%). Other Gram positive bacteria, including Streptococcus pneumoniae (7%), Streptococcus pyogenes (4%), Staphylococcus aureus (9%) and Enterococcus spp. (2%) accounted for 22% of the isolates. Aerobic Gram negative and anaerobic bacteria had an isolation rate of 35% and 16%, respectively.

Table 2. The bacteriology of Community-Acquired Pleural Infection (CAPI).

 

 

Ahmed
et al (2006)

Maskell
et al (2006)

 

Liang
et al (2007)

Isolates (n)

16

336

55

Aerobic Gram (+)

12

207

27

Streptococcus spp

11

176

21

 S. pneumoniae

1

71

4

 S. pyogenes

2

9

2

 S. viridans

0

0

15

 other streptococci

1

16

0

Staph. aureus

0

27

5

 MSSA

 

20

 

 MRSA

 

7

 

Enterococcus spp

0

4

1

Other Gram (+)

0

0

0

Aerobic Gram (-)

1

29

19

Klebsiella pn

1

0

5

Pseudomonas spp

0

3

1

Escherichia coli

0

11

3

Enterobacter spp

0

5

1

Proteus spp

0

6

3

S.maltophilia

0

0

1

Acinetobacter spp

0

0

1

other Gram (-)

0

4

4

Aerobic

1

67

9

Bacteroides spp

0

16

1

Prevotella spp

0

13

1

Fusobacterium

0

19

1

Peptostreptococcus

0

9

4

Anaerobic streptococci

0

0

0

other anaerobic

0

10

2

Hospital-acquired Pleural Infection (HAPI)

The most commonly cultured microorganism in pleural fluid from patients with HAPI is Staphylococcus aureus, according to two recent studies that focussed on that specific population2, 25, and in most cases MRSA is implicated. The cumulative findings from these studies are shown in Table 3. Once again, it seems that the bacteriology of pleural infection markedly differs from that of pneumonia, even in the hospital setting.

In the microbiology of HAPI observed in MIST12, aerobic Gram positive bacteria comprised 67% of the isolates. Staphylococcus aureus and enterococci were the most prevalent bacteria accounting for 35% and 12% of the isolates, respectively. Aerobic Gram negative bacteria, including five different organisms with an isolation rate of <5%, accounted for 23% of the isolates, and only 8% of the pleural infections were due to anaerobic organisms.

In the study of Tu et al25 of pleural infection in 32 patients with HAPI admitted to the MICU during a 30-month period 45 different microorganisms were isolated. Although, aerobic Gram negative bacteria accounted for 64% of the isolates, no single Gram negative organism of the nine different ones identified had an isolation rate of >13%. Staphylococcus aureus, which was the most commonly isolated organism was the causative agent in 20% of the pleural infections, and anaerobes were found in 8% of the isolates.

The «Streptococcus milleri group»

«Streptococcus milleri» has been found to be the most common isolate in CAPI, but not in HAPI. However, the fact that CAPI has more than twice the incidence of HAPI brings the «Streptococcus milleri group» into the first place among all isolates associated with pleural infection4. This is why the most interesting characteristics of this microorganism will be presented here.

«Streptococcus milleri» as a species

Until the late 1980's, the diverse Streptococcus species were identified and classified, based upon a few characteristics that were easily determined by microbiologists and which included their action on blood agar and serological traits. However, when more characteristics were examined, it was discovered that for some streptococci, haemolysis and serological reactions were inadequate as methods for their discrimination. The «Streptococcus milleri group» is probably the most characteristic example of this situation26.

Table 3. The bacteriology of Hospital-Acquired Pleural Infection (HAPI).

 

Tu et al

(2006)

Maskell et al

(2006)

Isolates (n)

45

60

Aerobic Gram (+)

12

40

Streptococcus spp

0

11

S. pneumoniae

0

3

S. pyogenes

0

0

S. viridans

0

0

other streptococci

0

4

Staph. aureus

9

21

MSSA

 

6

MRSA

 

15

Enterococcus spp

3

7

Other Gram (+)

0

0

Aerobic Gram (-)

29

14

Klebsiella pn

4

0

Pseudomonas spp

6

3

Escherichia coli

3

2

Enterobacter spp

2

1

Proteus spp

2

2

S. maltophilia

1

0

Acinetobacter spp

4

0

other Gram (-)

0

6

Aerobic

2

5

Bacteroides spp

1

1

Prevotella spp

0

1

Fusobacterium

0

1

Peptostreptococcus

1

0

Anaerobic streptococci

0

0

other anaerobic

0

2

The name «Streptococcus milleri» was first used by Guthof 27 in 1956 to describe non-haemolytic streptococci isolated from oral infections, and was chosen to honor the oral microbiologist WD Miller. Subsequently, Colman and Williams28 in 1972 proposed the inclusion of Guthof's strains along with other non-haemolytic strains with common physiological characteristics and cell wall composition. They, however, commented that their «Streptococcus milleri» strains were serologically heterogeneous and could demonstrate Lancefield group A, C, F or G antigens, various type antigens or no detectable antigen. Furthermore, they found that non-haemolytic «Streptococcus milleri» strains were physiologically similar to some beta-haemolytic streptococci, and therefore suggested that the «Streptococcus milleri» designation could also be applied to these beta-haemolytic strains. Thus, the concept of the species «Streptococcus milleri» that they proposed was novel; they included serologically diverse isolates with various haemolytic reactions in a single species defined by physiological similarities.

In 1977, Facklam29 proposed that isolates referred to as «Streptococcus milleri» should be divided on the basis of lactose fermentation into two species: «Streptococcus intermedius» (lactose fermenting) and «Streptococcus anginosus-constellatus» (unable to ferment lactose), but his study, however, did not include beta-haemolytic «Streptococcus milleri» strains. In 1984, in Facklam's revised nomenclature30, lactose positive «Streptococcus milleri» was called Streptococcus intermedius, lactose negative strains were called Streptococcus constellatus and beta-haemolytic strains were referred to as Streptococcus anginosus. Three years later, Coykendall et al31, based on DNA hybridization studies, proposed the re-unification of the various types of streptococci known as «Streptococcus milleri» into a single species named Streptococcus anginosus. In his most recent revised nomenclature, Facklam32, accepted the name of Streptococcus anginosus for a group of Streptococci viridans that includes three distinct species (Streptococcus anginosus, Streptococcus constellatus and Streptococcus intermedius) and other subspecies. While Facklam's nomenclature is generally used in the United States, European authors usually prefer the «Streptococcus milleri» designation 26.

The bacteriologic characteristics of the «Streptococcus milleri group»

Regardless of nomenclature, the recognition of organisms referred to as «Streptococcus milleri» is usually based on their ability to produce acetonin from glucose, to ferment lactose, trehalose, salicin and sucrose, and to hydrolyze esculin and arginin. They tend to form microcolonies (0.5 mm in diameter) which have only one half to two thirds of the diameter of colonies of other streptococci. Sometimes they have a distinct caramel odour. Carbon dioxide stimulates the growth, or is required for the growth of some strains and because of this, the isolates are sometimes mistaken for anaerobic streptococci33. Gram staining of the members of the «Streptococcus milleri group» reveals Gram-positive spherical or ovoid cells that form chains or pairs. Despite their physiological similarities, the various «Streptococcus milleri» organisms present great phenotypic heterogeneity, demonstrating various patterns of haemolysis (α, β and γ), Lancefield grouping (A, C, F, G and non-typeable) and ability to ferment various sugars32.

Differentiation of the members of «Streptococcus milleri group»

Once the presumptive identification of «Streptococcus milleri» has been made, microbiologists can relatively easily differentiate between the three members of this bacterial group, based on phenotypic characteristics34. A variety of commercial systems are also available for this purpose, some of which are in high agreement with the conventional methods35. In addition PCR assays that have been developed for the identification of Streptococci viridans, could be helpful in the differentiation between Streptococcus intermedius, Streptococcus constellatus and Streptococcus anginosus36-38.

The Clinical significance of the «Streptococcus milleri group»

«Streptococcus milleri» is a common commensal organism in humans, found in the normal flora of the respiratory tract, the gastrointestinal tract and the vagina. In 15-30% of normal people, it also has remarkable potential as a pathogen 39-41 and plays an important role in infections of internal organs and certain body fluids. It was found to be the most frequent isolate in intracranial pus drained from CNS abscesses42. In other reports, it has been implicated as a cause of meningitis and brain abscesses43-45. It has also been found as a pathogen in pyogenic liver abscesses46-49 and appendicitis50,51. Moreover, a specific mannitol-fermenting strain of «Streptococcus milleri» frequently isolated from the female genital tract, has been implicated in two cases of neonatal sepsis52. Although it is not a common cause of endocarditis and bacteraemia, its isolation from blood should alert clinicians to the possible presence of an abscess as the source of bacteraemia26,53-56. Whiley et al have stated that there tends to be an association between the clinical system source and the three species included in the «Streptococcus milleri» group. Streptococcus anginosus is commonly isolated from urogenital and gastrointestinal sources, Streptococcus constellatus is often isolated from respiratory and many other sources, while Streptococcus intermedius are more commonly isolated from brain and liver abscesses40.

The incidence of thoracic infections due to «Streptococcus milleri» ranges between 10-32% of all «Streptococcus milleri» infections55-59 and between 24-57% of all suppurative thoracic infections60,61. Empyema is the most common type of thoracic infection caused by «Streptococcus milleri », accounting for up to 78% of the cases56, 58, 62-64. Other thoracic manifestations include mediastinitis and lung abscess. The microorganisms can reach the thoracic cavity by aspiration of oral secretions, by direct implantation after trauma or surgery, through extension by contiguity, or by haematogenous dissemination60.

Pathogenicity

The tendency of the «Streptococcus milleri group» to cause putrifying infections in humans has been long recognized42, 43, 46-49, 57. The exact mechanisms of the pathogenic process have not been established, but recent research has revealed that the «Streptococcus milleri» strains have multiple pathogenic properties (Table 4).

Firstly, it has been shown that members of the «Streptococcus milleri group» possess certain unique growth characteristics, including the ability to grow well in acidic environments such as produced in empyemas and abscesses65. Moreover, in vivo and in vitro evidence suggests that E. corrodens, Fusobacterium nucleatum and Prevotella intermedia along with «Streptococcus milleri» may work synergistically in the production of pyogenic infections66-68. The organisms of the «Streptococcus milleri group» use a chemical language of signalling molecules in a process called quorum sensing (QS). More specifically, QS is the cell population density-dependent regulation of gene expression by small signalling molecules, called autoinducers (AI). Although most AIs promote intra-species communication, AI-2 allows communication between species as well. It has been shown that AI-2 affects the antibiotic susceptibility of «Streptococcus milleri» and it could also play a role in synergistic infections69.

Table 4. The virulence factors of the «Streptococcus milleri group»

Growth characteristics

Intrinsic factor

Immunologic factors

  • ability to grow in acidic environment
  • more rapid replication in mixed infections
  • quorum sensing (QS) / antibiotic resistance
    - AI-2 signalling

 

  • adhesins
    - Ag I/II
  • polysaccharide capsule
  • pyrogenic exotoxins
    - intermedilysin
  • hydrolytic enzymes
    -  hyaluronidase
    -  deoxyribonuclease
    -  chondroitin sulfatase
    -  sialidase
  • lymphocyte apoptosis
    - superantigens
  • lymphocyte proliferation
    - 90 kDa protein
  • cytokine production by monocytes
    - Si-HLP
  • phagocytosis by PMN

 

A variety of intrinsic factors could also be responsible for the distinctive pathogenecity of this bacterial group. All streptococci, including the «Streptococcus milleri group», express a number of adhesins on their cell surface that facilitate adherence to various substrates70. Attachment and colonization of damaged tissues is probably necessary before the tissue invasion by bacteria, during the development of infection71. Antigen I/II (Ag I/II) constitute a family of structurally and antigenically related cell surface proteins found in Streptococcus intermedius and in several other streptococci. Ag I/II shows multifunctional activities, including binding to soluble extracellular matrix glycoproteins and host cell receptors, coaggregation with other bacteria, interactions with salivary glycoproteins, and activation of monocytic cells. The success of streptococcal colonization and survival within the human host may be related to Ag I/II72. All members of the «Streptococcus milleri group» are able to bind to fibronectin via this cell surface protein, and some can also bind to platelet-fibrin, fibrin clots and fibrinogen71, 73. Although not proven yet, this property could be responsible for pleural adhesions during the course of pleural infection. In addition, a polysaccharide capsule that provides the ability to escape phagocytosis is a frequent finding in «Streptococcus milleri» strains and allows them to replicate after attaching to damaged tissues74.

The production of pyrogenic exotoxins is a common feature among streptococci75. Intermedilysin is the only human cell-specific cytolytic toxin that has been reported with regard to «Streptococcus milleri». It is produced only by Streptococcus intermedius and has a potent haemolytic effect on human erythrocytes76. Members of the «Streptococcus milleri group» also produce a variety of hydrolytic enzymes, such as hyaluronidase, deoxyribonuclease, chondroitin sulfatase and sialidase, which are important in tissue liquefaction, abscess formation and spread of the infection to the surrounding tissues77-79.

There are some interesting reports concerning the interaction of «Streptococcus milleri» with host's immune system. Superantigens should probably be considered one of the most important virulence factors of the «Streptococcus milleri group». These consist of a diverse group of molecules that can stimulate specific lymphocyte subsets and cause their death through apoptosis80. A 90-kDa protein that suppresses lymphocyte and fibroblast proliferation has also been recovered from Streptococcus intermedius81. Another group of proteins called histone-like DNA binding proteins (HLPs), was studied in Streptococcus intermedius (Si-HLP) and found to stimulate the production of pro-inflammatory cytokines82. Finally, it has been shown that members of the «Streptococcus milleri group» can suppress bacterial phagocytosis by polymorphonuclear leukocytes83,84.

Antibiotic selection

Members of the «Streptococcus milleri group» used to be penicillin-sensitive with minimal inhibitory concentrations (MIC) to penicillin G <0.06 μg/ml. This was so until the early 1980's85, 86, since when increasing in vitro resistance to penicillin G and other β-lactam agents has been reported, especially among Streptococcus anginosus and Streptococcus intermedius strains. Resistance to erythromycin and clindamycin has also been described87, 88. In clinical practice, infections due to «Streptococcus milleri» have responded well to cephalosporins89. Thus the combination of a cephalosporin or aminopenicillin with a β-lactamase inhibitor is a reasonable antibiotic selection in order to cover for penicillin-resistant strains of the «Streptococcus milleri group». The combination of these antibiotics with anaerobic cover provides adequate empirical treatment in CAPI90. In patients with β-lactam allergies vancomycin and clindamycin are alternative choices. The newer quinolones and quinupristin-dalfopristin may also be useful against «Streptococcus milleri» infections91,92. It should be emphasized, however, that even when the appropriate antibiotic treatment is chosen, the majority of patients with «Streptococcus milleri» infections will require operative intervention for definitive therapy93. In case of HAPI the antibiotic regimen should include a broad-spectrum antibiotic such as one of the carbapenems or anti-pseudomonal penicillin, combined with an agent against MRSA90.

Conclusion

Gram positive bacteria are the main organisms responsible for pleural infections. The «Streptococcus milleri group» is the predominant isolate in CAPI, while Staphylococcus aureus is most commonly isolated in the hospital setting. Given the higher incidence of CAPI, «Streptococcus milleri» is probably the most common isolate overall in pleural infections. This increased frequency is probably a result of the unique characteristics of this bacterial group that make possible the production of putrifying and necrotizing infections. Drainage of the infected pleural fluid and antibiotic administration are essential components of the management of pleural infection. Knowledge of the current bacteriology of pleural infections is an important adjunctive tool in the management of this disease and antibiotic selection for empirical treatment should definitely cover the «Streptococcus milleri group» of microorganisms.

References

    1. Light RW. Parapneumonic Effusions and Empyema In: Light RW. (editor). Pleural Diseases, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2007, pp. 179-210.

    2. Maskell NA, Batt S, Hedley EL, Davies CW, Gillespie SH, Davies RJ. The bacteriology of pleural infection by genetic and standard methods and its mortality significance. Am J Respir Crit Care Med, 2006; 174(7): 817-23.

    3. Lin YC, Chen HJ, Liu YH, Shih CM, Hsu WH, Tu CY. A 30-month experience of thoracic empyema in a tertiary hospital: emphasis on differing bacteriology and outcome between the medical intensive care unit (MICU) and medical ward. South Med J, 2008; 101(5): 484-9.

    4. Rahman NM, Chapman SJ, Davies RJ. The approach to the patient with a parapneumonic effusion. Clin Chest Med, 2006; 27(2): 253-66.

    5. Colice GL, Curtis A, Deslauriers J, et al. Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline. Chest, 2000; 118(4): 1158-71.

    6. Maskell NA, Davies CW, Nunn AJ, et al. U.K. Controlled trial of intrapleural streptokinase for pleural infection. N Engl J Med, 2005; 352(9): 865-74.

    7. Ahmed RA, Marrie TJ, Huang JQ. Thoracic empyema in patients with community-acquired pneumonia. Am J Med, 2006; 119(10): 877-83.

    8. Davies CW, Kearney SE, Gleeson FV, Davies RJ. Predictors of outcome and long-term survival in patients with pleural infection. Am J Respir Crit Care Med, 1999; 160(5 Pt 1): 1682-7.

    9. Ferguson AD, Prescott RJ, Selkon JB, Watson D, Swinburn CR. The clinical course and management of thoracic empyema. QJM, 1996; 89(4): 285-9.

  10. Finland M,Barnes MW. Changing ecology of acute bacterial empyema: occurrence and mortality at Boston City Hospital during 12 selected years from 1935 to 1972. J Infect Dis, 1978; 137(3): 274-91.

  11. Bartlett JG, Gorbach SL, Thadepalli H, Finegold SM. Bacteriology of empyema. Lancet, 1974; 1(7853): 338-40.

  12. Varkey B, Rose HD, Kutty CP, Politis J. Empyema thoracis during a ten-year period. Analysis of 72 cases and comparison to a previous study (1952 to 1967). Arch Intern Med, 1981; 141(13): 1771-6.

  13. Brook I,Frazier EH. Aerobic and anaerobic microbiology of empyema. A retrospective review in two military hospitals. Chest, 1993; 103(5): 1502-7.

  14. Light RW. Clinical Manifestations and Useful Tests. In: Light RW. (editor). Pleural Diseases, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA, 2007, pp. 73-108.

  15. Schultz KD, Fan LL, Pinsky J, et al. The changing face of pleural empyemas in children: epidemiology and management. Pediatrics, 2004; 113(6): 1735-40.

  16. Thadepalli H,Gangopadhyay PK. Rapid diagnosis of anaerobic empyema by direct gas-liquid chromatography of pleural fluid. Chest, 1980; 77(4): 507-13.

  17. Lampe RM, Chottipitayasunondh T, Sunakorn P. Detection of bacterial antigen in pleural fluid by counterimmunoelectrophoresis. J Pediatr, 1976; 88(4 Pt. 1): 557-60.

  18. Saito T, Iinuma Y, Takakura S, et al. Feasibility of flow cytometry for the detection of bacteria from body fluid samples. J Infect Chemother, 2005; 11(5): 220-5.

  19. Ploton C, Freydiere AM, Benito Y, et al. Streptococcus pneumoniae thoracic empyema in children: rapid diagnosis by using the Binax NOW immunochromatographic membrane test in pleural fluids. Pathol Biol (Paris), 2006; 54(8-9): 498-501.

  20. Saglani S, Harris KA, Wallis C, Hartley JC. Empyema: the use of broad range 16S rDNA PCR for pathogen detection. Arch Dis Child, 2005; 90(1): 70-3.

  21. Lin YC, Tu CY, Chen W, et al. An urgent problem of aerobic gram-negative pathogen infection in complicated parapneumonic effusions or empyemas. Intern Med, 2007; 46(15): 1173-8.

  22. Bilgin M, Akcali Y, Oguzkaya F. Benefits of early aggressive management of empyema thoracis. ANZ J Surg, 2006; 76(3): 120-2.

  23. Liang SJ, Chen W, Lin YC, et al. Community-acquired thoracic empyema in young adults. South Med J, 2007; 100(11): 1075-80.

  24. Jerng JS, Hsueh PR, Teng LJ, Lee LN, Yang PC, Luh KT. Empyema thoracis and lung abscess caused by viridans streptococci. Am J Respir Crit Care Med, 1997; 156(5): 1508-14.

  25. Tu CY, Hsu WH, Hsia TC, et al. The changing pathogens of complicated parapneumonic effusions or empyemas in a medical intensive care unit. Intensive Care Med, 2006; 32(4): 570-6.

  26. Ruoff KL. Streptococcus anginosus («Streptococcus milleri»): the unrecognized pathogen. Clin Microbiol Rev, 1988; 1(1): 102-8.

  27. Guthof O. [Pathogenic strains of Streptococcus viridans; streptocci found in dental abscesses and infiltrates in the region of the oral cavity.]. Zentralbl Bakteriol [Orig], 1956; 166(7-8): 553-64.

  28. Wannamaker LW, Matsen JM. Streptococci and streptococcal diseases; recognition, understanding, and management. Academic Press, New York, 1972

  29. Facklam RR. Physiological differentiation of viridans streptococci. J Clin Microbiol, 1977; 5(2): 184-201.

  30. Facklam RR, Rhoden DL, Smith PB. Evaluation of the Rapid Strep system for the identification of clinical isolates of Streptococcus species. J Clin Microbiol, 1984; 20(5): 894-8.

  31. Coykendall AL WP, Gustafson KB. Genetic similarities among four species of Streptococcus. S.milleri, S.anginosus, S.constellatus and S.intermedius. Int J Syst Bacteriol, 1987; 37: 222-228.

  32. Facklam R. What Happened to the Streptococci: Overview of Taxonomic and Nomenclature Changes. Clinical Microbiology Reviews, 2002; 15(4): 613-630.

  33. Ball LC,Parker MT. The cultural and biochemical characters of Streptococcus milleri strains isolated from human sources. J Hyg (Lond), 1979; 82(1): 63-78.

  34. Whiley RA, Fraser H, Hardie JM, Beighton D. Phenotypic differentiation of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus strains within the «Streptococcus milleri group». J Clin Microbiol, 1990; 28(7): 1497-501.

  35. Flynn CE,Ruoff KL. Identification of «Streptococcus milleri» group isolates to the species level with a commercially available rapid test system. J Clin Microbiol, 1995; 33(10): 2704-6.

  36. Sultana F, Kawamura Y, Hou XG, Shu SE, Ezaki T. Determination of 23S rRNA sequences from members of the genus Streptococcus and characterization of genetically distinct organisms previously identified as members of the Streptococcus anginosus group. FEMS Microbiol Lett, 1998; 158(2): 223-30.

  37. Jacobs JA, Schot CS, Bunschoten AE, Schouls LM. Rapid species identification of «Streptococcus milleri» strains by line blot hybridization: identification of a distinct 16S rRNA population closely related to Streptococcus constellatus. J Clin Microbiol, 1996; 34(7): 1717-21.

  38. Garnier F, Gerbaud G, Courvalin P, Galimand M. Identification of clinically relevant viridans group streptococci to the species level by PCR. J Clin Microbiol, 1997; 35(9): 2337-41.

  39. Poole PM,Wilson G. Occurrence and cultural features of Streptococcus milleri in various body sites. J Clin Pathol, 1979; 32(8): 764-8.

  40. Whiley RA, Beighton D, Winstanley TG, Fraser HY, Hardie JM. Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus (the Streptococcus milleri group): association with different body sites and clinical infections. J Clin Microbiol, 1992; 30(1): 243-4.

  41. Parkins MD, Sibley CD, Surette MG, Rabin HR. The Streptococcus milleri group--an unrecognized cause of disease in cystic fibrosis: a case series and literature review. Pediatr Pulmonol, 2008; 43(5): 490-7.

  42. de Louvois J. Bacteriological examination of pus from abscesses of the central nervous system. J Clin Pathol, 1980; 33(1): 66-71.

  43. Melo JC,Raff MJ. Brain abscess due to Streptococcus MG-intermedius (Streptococcus milleri). J Clin Microbiol, 1978; 7(6): 529-32.

  44. Koepke JA. Meningitis Due to Streptococcus Anginosus (Lancefield Group F). JAMA, 1965; 193: 739-40.

  45. Tecson-Tumang F, Sen P, Kapila R. Fatal Streptococcus MG-intermedius (Streptococcus

References